Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• was run in the absence of azide using optimized conditions (see Supporting Information File 1, mechanistic study, section 8). However, its further characterization was not possible because it disappeared upon workup. Finally, a 2D NOESY experiment was utilized to confirm the regiochemistry of 4-(1-(4

• Equiv of CuSO4 was used as an additive. bModified reaction conditions for benzyl azides: 1 (1 equiv), 2 (1.5 equiv) 0.4 equiv of LiHMDS (1 M in THF), morpholine (0.34–0.4 M), 110 °C, 72 h. Time course profile monitored by 19F NMR spectroscopy. NOESY of 4e confirming the regiochemistry of the product

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• − 99Val) provided the needed sequence information for the structure of compound 1. Stereochemistry determination Historically, the determination of the regiochemistry of enantiomeric amino acid residues within natural product peptides has proved challenging sometimes requiring the strenuous efforts of de

• novo total synthesis or degradation. This is because in natural product peptides both the ᴅ- and ʟ-forms of the different amino acids may be incorporated into the peptide structure. In order to determine the regiochemistry of the Val, Leu, Asp, and Glu amino acid residues in compound 1, we deployed the

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• single product, and the regiochemistry of 5-selanyltriazole 8 was confirmed by single crystal X-ray analysis (see Supporting Information File 3). The reaction performed using 10 mol % of CuI and PMDETA as catalytic system afforded only a small amount of product 8 (12%). Based on the results obtained in

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• attractive cyclization and annulation of 3,5-unsubstituted, 4-substituted indoles have been reported in the recent past. Herein, we summarize these literature reports, with a special attention on the regiochemistry. Noteworthy is that although three reviews on the synthesis of 3,4-fused indoles have been

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• (15e, 15f, 15h). Sensitive functional groups like alkyl iodides were tolerated in the reaction, although product yields were slightly diminished. The relative stereo- and regiochemistry of the adducts was confirmed through NMR experiments and X-ray crystallography (15h) [67]. We next sought to

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• , consistent with the spectra of 1,4-disubstituted triazole regiochemistry [22]. The final step was carried out in CH3OH/triethylamine/H2O 4:1:5 [26], followed by triethylammonium ion exchange for Na+ upon treatment with Amberlite IR 120 (Na+), to give the fully deprotected derivatives 3a–h in excellent yields

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• elodeoidins, from the herb Hypericum elodeoides [28]. The authors proposed that these molecules derived from common acylfilicinic acid precursors 87 through two distinct pathways based on the regiochemistry of an oxidation–α-ketol rearrangement sequence (Figure 17). If oxidation occurs at C3, then a

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• ) preference for the formation of the corresponding N-2 regioisomer 11 (ratio N-1:N-2 = 1:2.5) rather than the desired N-1 regioisomer. To assign the regiochemistry of isolated N-1 and N-2 substituted indazole isomers, a combination of one and two-dimensional NMR experiments (particularly, heteronuclear

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• (55%) yield. Unfortunately, the reaction was not successful with dimedone (2d), 1,3-indanedione (2e) and acyclic 1,3-dicarbonyl compounds such as acetylacetone (2e) and ethyl acetoacetate (2f). The structure and regiochemistry of all the products were confirmed by detailed analysis of their spectral

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• by nucleophiles. As is the case for the nucleophilic opening of epoxides, the regiochemistry of this process is often controlled very effectively by the combined steric and electronic effects of the substituents attached to the ring, with a spectrum of SN1 and SN2-like reactivity possible. Several

Exploring the possibility of using fluorine-involved non-conjugated electron-withdrawing groups for thermally activated delayed fluorescence emitters by TD-DFT calculation

• Dongyang Chen and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2021, 17, 210–223, doi:10.3762/bjoc.17.21

• emitters possessing a diphenyltriazine as the acceptor and different regiochemistry of the carbazole donors; the ΔESTs increased to 0.10 eV for 2,4-2CzTRZ and 0.29 eV for 3,4-2CzTRZ. The single crystal structure of 2,6-2CzTRZ revealed a highly twisted structure with large torsions (81.0o and 76.3o) between

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• to the formation of two regioisomers, but interestingly, the ratio of the 7-CF2H- and 9-CF2H-isomers varied broadly from 1:2 [22] to 3:2, depending on the reaction conditions and the source of difluorocarbene [11]. Mechanism, regiochemistry, and rotation barriers of the CH(CF3)2 group The mechanism

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• stereochemical outcome of the overall process. A carbon monoxide ligand then undergoes migratory insertion into one of the Co–C bonds in cobaltacycle V, followed by reductive elimination to release the final product (Scheme 3). As mentioned above, the regiochemistry of this transformation is, in most cases

• , for alkynes 58b,c the opposite regiochemistry was found. Finally, the use of alkyne 58d with two electron-withdrawing groups resulted in the regioselective formation of product 59d in excellent yield, indicating an inherent trend of the fluoroalkyl group to occupy the α-position regardless of the

• the regiochemistry for terminal alkynes, affording the products substituted at the β-position. This regiochemistry switch might be regarded as the Holy Grail in Pauson–Khand chemistry. The synthetic potential of this methodology was demonstrated by the formal total synthesis of α-cuparenone [74][75

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• regiochemistry of dimers 3a,b and 8a,b. Acid-catalyzed transformation of unsubstituted ortho-(pivaloylaminomethyl)benzaldehyde (1e) In order to reduce the number of possible dimer-like products, we carried out the reaction with unsubstituted o-(pivaloylaminomethyl)benzaldehyde (1e). Since the positional change

Regioselectivity of glycosylation reactions of galactose acceptors: an experimental and theoretical study

• Enrique A. Del Vigo,
• Carlos A. Stortz and
• Carla Marino

Beilstein J. Org. Chem. 2019, 15, 2982–2989, doi:10.3762/bjoc.15.294

• and one free hydroxy unit in order to achieve glycosylations with respect to the desired regiochemistry. The synthesis of such building blocks is usually the most time-consuming process of oligosaccharide synthesis [2][3]. The knowledge and control of glycosylation regioselectivity of building blocks

Experimental and computational electrochemistry of quinazolinespirohexadienone molecular switches – differential electrochromic vs photochromic behavior

• Eric W. Webb,
• Jonathan P. Moerdyk,
• Kyndra B. Sluiter,
• Benjamin J. Pollock,
• Amy L. Speelman,
• Eugene J. Lynch,
• William F. Polik and
• Jason G. Gillmore

Beilstein J. Org. Chem. 2019, 15, 2473–2485, doi:10.3762/bjoc.15.240

• long-wavelength isomers, we have found that a second, distinct long-wavelength isomer is produced electrochemically. This different long-wavelength isomer arises from a difference in the regiochemistry of spirocyclic ring-opening. The structures of both long-wavelength isomers were ascertained by

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• compounds and because it decreases with the distance between the substituents, it is barely observable for the AD substitution. For the unambiguous verification of regiochemistry, however, conversion of the capped β-CDs to the corresponding diphenylthio derivatives is needed, followed by Taka-amylase

• identification, the authentic diazido compounds with known regiochemistry were synthesized using the appropriately spaced disulfonate capping agent, followed by azide opening of the cap and by chromatographic purification of the diazidated fractions [11][12] (reference reactions 1–3, Scheme 1). Direct

• ). Analysis of regiochemistry of homo-difunctionalized β-cyclodextrins by full NMR spectral assignment NMR structural analysis was performed on the ditosyl derivatives, precursors of the corresponding diazido compounds. There are two factors that warrant large signal dispersion in the 1H NMR spectra of

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• desired product 5a was obtained in 67% yield, together with an oxidized ring opened side product 6 in 20% yield. The overall yield of 5a after two steps was 48%, considering that the 3-nitro-2H-chromene (3) was obtained in a yield of 71%. We continued our studies by verifying the obtained regiochemistry

• Information File 1, Figure S1 for NMR comparison), we can make unambiguous conclusions about the regiochemistry of the synthesized compounds 5a, 10 and 11 (Scheme 2). As the product contains a stereocenter, there is a possibility to see diastereotopic splitting of the benzylic protons. In the spectrum of the

• polar triazolium annulated chromene. Conclusion We developed a sequential one-pot three-component reaction to access a variety of novel triazolochromenes avoiding the purification of intermediate 3-nitro-2H-chromenes. The regiochemistry of the reaction was determined and proven, followed by a scope

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• offer no direct explanation for the observed regioselectivity, the mechanism of the reaction could provide some insight. The key step of the reaction, which sets the regiochemistry of the product is seen in Figure 10. The intermediate cation radical Int 10 and the stability of the positive charge in the

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• compound that ionizes in liquid SO2 to the cation 134b. Treatment of cations with nucleophiles that are preferably added to the benzylic position (C-5 or C-9) yielded chloro- and bromo-5H-benzo[7]annulenes 136–143. According to Hückel molecular orbital (HMO) calculations, this observed regiochemistry is

Electrophilic trifluoromethylselenolation of terminal alkynes with Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate

• Clément Ghiazza,
• Anis Tlili and
• Thierry Billard

Beilstein J. Org. Chem. 2017, 13, 2626–2630, doi:10.3762/bjoc.13.260

• . Further, a high regioselectivity is observed but, surprisingly, the anti-Markovnikov regioisomers were obtained. The stereochemistry and regiochemistry were confirmed thanks to the X-ray structure of compound 3a (Figure 1). From a mechanistic point of view, the reaction starts certainly with the

Synthesis, effect of substituents on the regiochemistry and equilibrium studies of tetrazolo[1,5-a]pyrimidine/2-azidopyrimidines

• Elisandra Scapin,
• Paulo R. S. Salbego,
• Caroline R. Bender,
• Alexandre R. Meyer,
• Anderson B. Pagliari,
• Tainára Orlando,
• Geórgia C. Zimmer,
• Clarissa P. Frizzo,
• Helio G. Bonacorso,
• Nilo Zanatta and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 2396–2407, doi:10.3762/bjoc.13.237

• (R in the 4-position of the ring), which was attributed to an equilibrium of azide–tetrazole. In the solid state, all compounds were found as 2-azidopyrimidines. The regiochemistry of the reaction and the stability of the products are discussed on the basis of the data obtained by density functional

• , SCXRD, PXRD, FTIR). Therefore, this study aims to (i) propose an efficient methodology for the synthesis of tetrazolo[1,5-a]pyrimidines substituted at the 5- and 7-positions of the heterocyclic ring; (ii) observe the regiochemistry of the cyclocondensation reaction and the effect of the substituent on

• enaminones [33][34]. This method provided good yields and regioselectivity using a simple catalyst and an IL as the solvent. Notably, not only the reaction time was short, but the purification process is simple. The regiochemistry of tetrazolo[1,5-a]pyrimidines The regiochemistry of tetrazolo[1,5-a

Regiodivergent condensation of 5-alkoxycarbonyl-1H-pyrrol-2,3-diones with cyclic ketazinones en route to spirocyclic scaffolds

• Alexey Yu. Dubovtsev,
• Maksim V. Dmitriev,
• Аndrey N. Maslivets and
• Michael Rubin

Beilstein J. Org. Chem. 2017, 13, 2179–2185, doi:10.3762/bjoc.13.218

• involving Michael addition followed by intramolecular transesterification. Remarkably, the resulting bridged products 12 have reversed regiochemistry as compared to the earlier-described cycloadducts 5 (Scheme 1). It should also be pointed out that all of these products were formed as single 10-endo

• elusive scaffold. Conclusion In conclusion, we discovered a new mode of cyclocondensations with “inverted” regiochemistry of addition, which involved the acid-catalyzed reaction of 5-alkoxycarbonyl-4-aroyl-1H-pyrrole-2,3-diones with cyclohexane-1,3-diones and lead to the formation of bridged 2,5

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• demonstrate the regiochemistry of the reaction. These cascade reactions proceed first through a Michael addition of the primary amine on the enone, followed by an intramolecular cyclization by the pyridine/pyrimidine nucleus. Unfortunately, no crystal structure could be obtained for the imidazopyrimidines and

Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

• Patrick T. Campos,
• Leticia V. Rodrigues,
• Andrei L. Belladona,
• Caroline R. Bender,
• Juliana S. Bitencurt,
• Fernanda A. Rosa,
• Davi F. Back,
• Helio G. Bonacorso,
• Nilo Zanatta,
• Clarissa P. Frizzo and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 257–266, doi:10.3762/bjoc.13.29

• intermediates, and from these data it was possible to explain the regiochemistry of the products obtained. Additionally, the data were a useful tool for elucidating the reaction mechanisms. Keywords: DFT-B3LYP; polyazaheterocycles; pyrazinone; pyrido[1,2-a]pyrimidinone; pyrimido[1,2-a]benzimidazole

• regiochemistry of the products [11]. Saiz et al. [14] synthesized 2-hydrazolyl-4-thiazolidinones with the aid of semi-empirical calculations (PM3 method). Through HOMO/LUMO energies, orbital coefficients, and charge distribution, a mechanism was proposed explaining the products observed. The authors claimed that

• the HOMO/LUMO energy gap is small and that the reaction between thiosemicarbazone and benzyl is kinetically favored, probably controlled by the frontier orbital component. Furthermore, calculations of HOMO and LUMO frontier orbital coefficients were used to prove the regiochemistry in cycloaddition